Org. Synth. 1951, 31, 11
DOI: 10.15227/orgsyn.031.0011
ARYLUREAS
II. UREA METHOD
p-ETHOXYPHENYLUREA
[Dulcin]
[Urea, p-ethoxyphenyl-]
1. Procedure
A mixture of 870 g. (5 moles) of p-phenetidine hydrochloride and 1.2 kg. (20 moles) of urea is placed in a 12-l. round-bottomed flask (Note 1). To this mixture are added 2 l. of water, 40 ml. of concentrated hydrochloric acid, and 40 ml. of glacial acetic acid, and the well-shaken suspension is heated to boiling. The dark purple solution thus obtained is boiled vigorously for 45–90 minutes until the reaction is complete. The liquid remains clear during the first half of the heating period. Separation of the product begins during the last half and proceeds with increasing rapidity until the entire contents of the vessel suddenly set to a solid mass. The source of heat is immediately withdrawn at this point (Note 2).
After cooling to room temperature, the product is broken up with the addition of 1–1.5 l. of water, filtered with suction, washed with cold water, drained, and dried. The crude p-ethoxyphenylurea is obtained in a yield of 740–810 g. (82–90%) as a nearly white to pale yellow solid (Note 3). This material may be purified by recrystallization from boiling water (Note 4), when minute white plates, m.p. 173–174°, are obtained. The method is applicable to the preparation of other substituted arylureas (Note 5).
2. Notes
1.
An
enameled-steel vessel of approximately 2-gal. capacity is suitable for carrying out this reaction.
2.
After removal of the heat source, a vigorous reaction may continue for a few minutes, and the reaction mixture tends to froth somewhat. It eventually sets to a sponge-like formation of a crystalline mass. In smaller-scale experiments the final stage of the reaction is more easily controlled. The checkers employed one-tenth the scale and conventional equipment.
3.
The crude product contains varying small quantities of the symmetrical disubstituted compound,
di-(p-ethoxyphenyl)urea [(p-C2H5OC6H4NH)2CO]. This substance is removed in the crystallization from water
(Note 4).
4.
To 1 l. of boiling water,
35 g. of crude p-ethoxyphenylurea is added. The bulk of the
urea dissolves readily, and the solution is decolorized by the addition of 3 g. of activated charcoal, boiled for 5 minutes, and quickly filtered with suction through a
pre-heated Büchner funnel. The colorless filtrate is slowly cooled to 0°, when lustrous minute plates of
p-ethoxyphenylurea separate. An
80% recovery of material having m.p.
173–174° is obtained. Prolonged boiling of the solution should be avoided, since slow conversion to
sym-di-(p-ethoxyphenyl) urea occurs under these conditions.
5.
p-Anisidine hydrochloride (0.5 mole), When boiled with the proportionate quantities of
urea and other reagents for 1 hour, gives
80–85% yields of
p-methoxyphenylurea. Owing to the greater solubility of this product in water, less of the material separates during the heating period, but satisfactory crystallization occurs when the reaction liquid is slowly cooled to 0°.
1-Amino-2-naphthol hydrochloride gives
72–87% yields of
1-(2-hydroxy-1-naphthyl)urea.
3. Discussion
p-Ethoxyphenylurea has been prepared by the action of
potassium cyanate on
p-phenetidine hydrochloride1 or
p-phenetidine acetate,
2 and by the interaction of
p-phenetidine with the following agents:
phosgene in
benzene or
toluene and treatment of the product with
ammonia;
3 urethan;
4 urea salts;
5 acetylurea;
6 and a mixture of
urea and
ammonium chloride.
7 It has been obtained from the reaction of phenetidine salts (usually the hydrochloride) with
urea,
5,8 or with a mixture of
sodium cyanide and sodium hypochlorite or peroxide.
9 p-Ethoxyphenylurea has also been prepared by heating
p-ethoxyphenylurethan and
ammonia to 100–180°;
4 by heating
di-(p-ethoxyphenyl)urea with
urea,
ammonium carbamate, commercial
ammonium carbonate,
10 or
ethanol and
ammonia;
11 by treating
ammonium p-ethoxyphenyldithiocarbamate with
lead carbonate in alcoholic solution;
12 by ethylating
p-hydroxyphenylurea;
13 and by the action of
ammonia on
p-ethoxyphenyl isocyanate.
14
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
Dulcin
sym-di-(p-ethoxyphenyl) urea
ethanol (64-17-5)
hydrochloric acid (7647-01-0)
acetic acid (64-19-7)
ammonium carbonate (506-87-6)
ammonia (7664-41-7)
Benzene (71-43-2)
ammonium chloride (12125-02-9)
sodium cyanide (143-33-9)
toluene (108-88-3)
phosgene (75-44-5)
urea (57-13-6)
ammonium carbamate (1111-78-0)
peroxide (7722-84-1)
sodium hypochlorite (7681-52-9)
potassium cyanate (590-28-3)
1-amino-2-naphthol hydrochloride (1198-27-2)
urethan (51-79-6)
1-(2-hydroxy-1-naphthyl)urea
acetylurea (591-07-1)
p-phenetidine (156-43-4)
p-phenetidine hydrochloride (637-56-9)
p-Methoxyphenylurea (1566-42-3)
p-Ethoxyphenylurea,
Urea, p-ethoxyphenyl- (150-69-6)
di-(p-ethoxyphenyl)urea
p-Anisidine hydrochloride (20265-97-8)
p-phenetidine acetate
p-ethoxyphenylurethan
ammonium p-ethoxyphenyldithiocarbamate
p-hydroxyphenylurea
p-ethoxyphenyl isocyanate (32459-62-4)
lead carbonate
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